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β‐Actin‐dependent global chromatin organization and gene expression programs control cellular identity
Author(s) -
Xie Xin,
Almuzzaini Bader,
Drou Nizar,
Kremb Stephan,
Yousif Ayman,
Farrants AnnKristin Östlund,
Gunsalus Kristin,
Percipalle Piergiorgio
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201700753r
Subject(s) - chromatin , microbiology and biotechnology , actin , gene expression , control (management) , identity (music) , gene , biology , genetics , computer science , physics , artificial intelligence , acoustics
During differentiation and development, cell fate and identity are established by waves of genetic reprogramming. Although the mechanisms are largely unknown, during these events, dynamic chromatin reorganization is likely to ensure that multiple genes involved in the same cellular functions are coregulated, depending on the nuclear environment. In this study, using high‐content screening of embryonic fibroblasts from a β‐actin knockout (KO) mouse, we found major chromatin rearrangements and changes in histone modifications, such as methylated histone (H)3‐lysine‐(K)9. Genome‐wide H3K9 trimethylation‐(Me)3 landscape changes correlate with gene up‐ and down‐regulation in β‐actin KO cells. Mechanistically, we found loss of chromatin association by the Brahma‐related gene ( Brg )/Brahma‐associated factor (BAF) chromatin remodeling complex subunit Brgl in the absence of β‐actin. This actin‐dependent chromatin reorganization was concomitant with the up‐regulation of sets of genes involved in angiogenesis, cytoskeletal organization, and myofibroblast features in β‐actin KO cells. Some of these genes and phenotypes were gained in a β‐actin dose‐dependent manner. Moreover, reintroducing a nuclear localization signal‐containing β‐actin in the knockout cells affected nuclear features and gene expression. Our results suggest that, by affecting the genome‐wide organization of heterochromatin through the chromatin‐binding activity of the BAF complex, β‐actin plays an essential role in the determination of gene expression programs and cellular identity.—Xie, X., Almuzzaini, B., Drou, N., Kremb, S., Yousif, A., Östlund Farrants, A.‐K., Gunsalus, K., Percipalle, P. β‐Actin‐dependent global chromatin organization and gene expression programs control cellular identity. FASEB J. 32,1296‐1314 (2018). www.fasebj.org